Introduction: Large number of patients with heart failure (HF) have left bundle branch block (LBBB). Most precise method for identification of intraventricular dyssynchrony is tissue Doppler imaging (TDI). Purpose of this research was to compare left ventricular (LV) mechanical dyssynchrony in LBBB patients with and without HF and to compare various methods of LV systolic dyssynchrony assessment by TDI. Materials and Methods: One hundred and sixteen patients with a diagnosis of LBBB were included in the study. All patients underwent conventional two-dimensional echocardiography for global LV function assessment. LV systolic dyssynchrony was measured by opposing wall delay, maximum delay, and Yu index. LBBB patients were grouped into four classes according to their LV function and the presence or absence of HF, normal LV function without HF (Group A), normal LV function with HF (Group B), LV dysfunction with HF (Group C), and LV dysfunction without HF (Group D). Results: LV systolic dyssynchrony was significantly higher (P <0.001) in Group C and D as compared to Group A and B. LV systolic dyssynchrony was significant higher in Group C and D as compared to Group A and B by using opposing wall delay (P <0.001), Yu index (P <0.001), and maximum delay (P <0.001) imaging criteria. Mean Yu index (P <0.001) and mean maximum delay (P <0.001) were significantly higher in Group C and D as compared to Group A and B. Conclusions: LV systolic dyssynchrony was more common in LBBB patients with LV dysfunction than those with normal LV function, irrespective of the presence or absence of HF.

There is increasing financial burden because of costs related to heart failure (HF) morbidity.[1],[2] Despite improved outcome based on pharmacological therapy primarily by inhibition of the renin–angiotensin–aldosterone system[3] and beta-blockade[4] the prognosis remains poor. Large number of patients with HF due to dilated cardiomyopathy had some intraventricular conduction defect in the majority of patients have left bundle branch block (LBBB).

Patients with conduction delays or disturbances in electrical activity experience delay in contraction between right and left ventricles, which decreases cardiac output.[5] Approximately 30% of patients with chronic HF have conduction pathway defects manifested by ventricular dyssynchrony.[6] Mechanical dyssynchrony refers to abnormal prolongation of the timing of contraction or relaxation between atrium and ventricle (atrioventricular dyssynchrony), between the right ventricle and left ventricle (interventricular dyssynchrony) or between different left ventricular (LV) segments (intraventricular or LV dyssynchrony).[7] Intraventricular dyssynchrony is probably the most important level of dyssynchrony evaluation. The most precise methodology for identification and quantification of the intraventricular level of dyssynchrony is probably tissue Doppler imaging (TDI).[8] Detailed echocardiographic assessment using tissue Doppler echocardiography has shown that patients with LBBB have marked intraventricular dyssynchrony that can be improved by biventricular pacing.[9]

Current American College of Cardiology guidelines consider cardiac resynchronization therapy (CRT) a Class I indication for patients with drug-refractory HF symptoms, LV ejection fraction (LVEF) 35% and wide QRS complex (>120 ms). Multiple single-center trials and cardiac resynchronization in HF trial have demonstrated that LV mechanical dyssynchrony indices (most of which are based on echocardiographic measures) have superior accuracy compared with LV electric dyssynchrony (based on QRS duration) to predict response to CRT and long-term outcome.[10],[11],[12] The purpose of this research is to compare LV mechanical dyssynchrony in LBBB patients with and without HF and to compare various methods of LV systolic dyssynchrony assessment by TDI.

Materials and Methods

One hundred and sixteen patients of >18 years of age admitted between June 2014 and May 2016 with a diagnosis of LBBB and ready to participate were included in this observational study. Permission was obtained from the ethics committee and scientific advisory committee of the institution. Written informed consent of the patients was obtained after explaining the details of the study, and the risk involved. The study included patients with LBBB (i.e., QRS duration >120 ms) with and without HF. Exclusion criteria were patient with LBBB and acute myocardial infarction, patients on CRT, patients with the acute coronary syndrome (≤4 weeks), rheumatic valvular heart disease, atrial fibrillation, or other atrial arrhythmias, previously implanted working pacemaker, and poorly echogenic patients in whom acquiring good quality images and a loop were not possible.

Based on previous study,[13] setting an alpha error at 0.05, and power at 80%, sample size of 116 patients was calculated by the formula.[14] Fifty-eight patients of LBBB with HF, of which 50 patients had LV systolic dysfunction and 8 patients had normal LV function, whereas 58 LBBB patients without HF, of which 50 patients had normal LV function and 8 patients had LV systolic dysfunction were included.

A detailed history of each patient with particular reference to demographic data, symptoms of HF, diabetes mellitus, hypertension, ischemic heart disease, cardiac arrhythmia was noted. Drug history, particularly about the HF medications was noted. Patients underwent general physical examination including pulse, blood pressure, respiratory rate, jugular venous pressure, and systemic examination of the cardiovascular system. In all patients, standard 12-lead electro cardiography (ECG) was taken, and QRS duration was measured from the widest QRS complex from lead 2, V1 and V6. ECG was recorded at the speed of 25 mm/s. HF was defined by Framingham HF diagnostic criteria.[15],[16]

All patients underwent conventional two-dimensional echocardiography for global LV function assessment by measuring LV end-diastolic and end systolic volumes and LVEF using the modified biplane Simpson's rule. Dyssynchrony assessment was done using the following parameters.

Color-coded tissue Doppler data acquisition was done. Three standard imaging planes were recorded as follows: apical 4-chamber view, apical 2-chamber view, and apical long-axis view. LV ejection interval was determined by using pulsed Doppler from an apical five-chamber or apical long-axis view where the LV outflow tract was seen and velocity recorded.

Color tissue Doppler data analysis

Color TDI data were analyzed offline using the customized software.[7] Measurements were made by two independent observers blinded to clinical outcome. Tissue velocity curves obtained by placing sample volumes in opposing basal and mid segments of septal, lateral, inferior, anterior and posterior walls were analyzed.

Data collected was entered into the Excel 2007 and analysis of data was performed using the Statistical Package for Social Sciences (SPSS) for Windows version 20, IBM Corporation, Chicago USA. Data on categorical variables arepresented as a percentage of cases. Data on continuous variables are presented as the mean ± SD Chi-square test or Fisher's exact test was used to compare qualitative variables, whereas ANOVA test was used to compare quantitative variables. The confidence limit for statistical significance was fixed at 95% level with value of P <0.05.

Results

A total number of 116 patient having complete LBBB fulfilling inclusion criteria were included in the present study. Five (4.3%) were <40 years, 21 (18.1%) were between 41 and 50 years, 41 (35.3%) were between 51 and 60 years, 34 (29.3%) were between 61 and 70 years of age, whereas 15 (12.9%) were >70 years of age. Seventy-three (62.9%) LBBB patients were male, whereas 43 (37.1%) were female.

LBBB patients were grouped into four classes according to their LV function and the presence or absence of HF.

Group A-Normal LV function without HF (50 patients)

Group B– Normal LV function with HF (8 patients)

Group C-LV dysfunction (LVEF ≤40%) with HF (50 patients)

Group D-LV dysfunction (LVEF ≤40%) without HF (8 patients).

As shown in [Table 1], there was no statistically significant difference in mean age, gender, H/O diabetes mellitus, H/O hypertension, the QRS duration between various subgroups of LV function and HF patients. LV systolic dyssynchrony was significantly higher (P <0.001) in Group C 42/50 (84%) and Group D 6/8 (75.0%) as compared to Group A 13/50 (26%) and Group B 4/8 (50%).

LV systolic dyssynchrony by TDI was said to be present when dyssynchrony was present with any one of the criteria of opposing wall delay, Yu index, and maximum delay. LV systolic dyssynchrony was present in 65 (56.0%) patients using all TDI criteria. LV systolic dyssynchrony was present in 55 (47.4%), 61 (52.6%), and 58 (50%) by opposing wall, Yu index, and maximum delay criteria, respectively. Mean LVEF was significantly higher in groups A (59.55) and B (59.63) as compared to Groups C (31.62) and D (38.38).

As depicted in [Table 2], LV systolic dyssynchrony was significantly higher in Group C and Group D as compared to Group A and Group B by using opposing wall delay (P <0.001), Yu index (P <0.001), and maximum delay (P <0.001) imaging criteria. Mean Yu index (P <0.001) and mean maximum delay (P <0.001) were significantly higher in Group C and Group D as compared to Group A and Group B.

Table 2: Various left ventricular systolic dyssynchrony criteria with subgroups

In all 116 patients with LBBB were included in the present study; they were grouped into four classes according to their LV function and the presence or absence of HF. These subgroups were analyzed for LV systolic dyssynchrony with various parameters of TDI. Results of the present study are compared and discussed with various studies.

Gorcsan et al.,[15] Cleland,[16] and Yu et al.[17] reported intraventricular systolic dyssynchrony in 66%, 60.4%, and 60.4%, respectively, in LBBB patients which were slightly higher than the present study 65/116 (56.0%). Prevalence of dyssynchrony among patients with LBBB with normal LV function without HF was 16% in study by Rao et al.[18] which was lower than the present study 13/50 (26%). De Sutter et al.[19] reported 45% prevalence of intraventricular dyssynchrony in HF patients with preserved LV function which is comparable to the present study 4/8 (50.0%). Bader et al.[20] and Rao et al.[18] in their study reported LV systolic dyssynchrony prevalence of 84% and 72%, respectively, in LBBB patients with LV dysfunction and HF which was similar to the present study 24/50 (84%), whereas De Sutter et al.[19] stated 46% prevalence of LV systolic dyssynchrony in HF patients with LV dysfunction which is less than the present study. Hara et al.[21] reported LV systolic dyssynchrony was present in 72% of the patients with LV dysfunction while in the present study 48/58 (82.8%) of the patients with LV dysfunction had LV systolic dyssynchrony. In the present study, the prevalence of LV dyssynchrony in patients with LV dysfunction was similar in studies conducted by Pitzalis et al.,[22] Ghio et al.[23] and Bleeker et al.[24] Prevalence of LV mechanical systolic dyssynchrony in the study of Perez de Isla et al.[25] by using TDI were similar in the present study.

Hara et al.[21] and Lotfi-Tokaldany et al.[13] reported that mean Yu index was 41 ± 17 ms and 42.33 ± 11.82 ms, respectively, in patients with LV dysfunction while in the present study, mean Yu index was 43.91 ± 9.03 ms in patients with LV dysfunction with HF. Prevalence of LV systolic dyssynchrony in patients with LV systolic dysfunction with HF was similar in both studies using Yu index and opposing wall delay criteria. Miyazaki et al.[26] reported mean Yu index of 48 ms in patients with normal LV function and 54 ms in patients with LV dysfunction, whereas the present study had mean Yu index of 31.6 ms in patients with normal LV function without HF and 43.91 ms in patients with LV systolic dysfunction and HF. In the present study mean Yu index in both the groups was lower than in the study by Miyazaki et al.[26] Yu et al.[10] reported mean Yu index among patients with LV dysfunction similar to the present study.

In the present study prevalence of intraventricular systolic dyssynchrony was 26% in patients with normal LV function by using Yu index criteria which were lower than reported by Miyazaki et al.[26] (85%) using the same criteria, but the prevalence of intraventricular systolic dyssynchrony was similar in both studies in patients with LV dysfunction using Yu index criteria. Prevalence of LV systolic dyssynchrony in study by Lotfi-Tokaldany et al.[13] using Yu index criteria was 73.0% in patients with LV dysfunction while it was 46/58 (79.3%) in the present study.

Miyazaki et al.[26] reported the prevalence of LV dyssynchrony in patients with normal LV function to be 60%–70% by opposing wall delay criteria, whereas in the present study, prevalence was 9/58 (15.5%) by applying same criteria in the same subgroup of patients. In the present study, prevalence of intraventricular systolic dyssynchrony in patients with LV dysfunction was 46/58 (79.3%) compared to a similar subgroup in the study by Miyazaki et al.[26] (73%–75%) and Lotfi-Tokaldany et al.[13] (35.1%–43.2%) with opposing wall delay criteria.

Prevalence of LV systolic dyssynchrony in the study by Lotfi-Tokaldany et al.[13] using the maximum delay in all LV segments was 67.6% in patients with LV dysfunction whereas 41/58 (70.7%) patients with LV dysfunction had LV systolic dyssynchrony by maximum delay criteria in the present study.

Prevalence of LV systolic dyssynchrony was similar in patients with LV dysfunction using various TDI dyssynchrony criteria, but patients without LV dysfunction had a higher prevalence of dyssynchrony in the study by Miyazaki et al.[26] than the present study. Prevalence of LV systolic dyssynchrony varied according to methods used in dyssynchrony assessment[21],[27] which substantiated the findings of current research.

Bader and et al.,[20] Perez de Isla et al.,[25] De Sutter et al.,[19] Pitzalis et al.,[22] Cleland et al.[16] and Bleeker et al.[24] stated that there was no significant difference in the systolic dyssynchrony in patients with QRS duration of 120–150 ms or >150 ms. The present study substantiated these findings. In the present study, LV dyssynchrony was more common in LBBB patients with LV dysfunction with HF than LBBB patients with normal LV function with HF. Study by De Sutter et al.[19] showed no difference in LV systolic dyssynchrony in LBBB patients with HF with or without LV dysfunction. Ghio et al.,[23] van Dijk et al.,[27] and Bleeker et al.[24] reported that LV systolic dyssynchrony was more common in LBBB patients with LV dysfunction and HF than those with normal LV function without HF irrespective of QRS duration. The present study substantiated these findings.

Limitations of the present study were only eight patients with normal LV function with HF and 8 patients with LV dysfunction without HF were included. Tissue velocities are dependent on multiple factors, therefore, the accuracy of tissue velocity mapping is low and it is less reproducible. ECG gating with tissue velocities was used in the present study due to nonavailability of speckle tracking echocardiography (STE) at our institute. STE is a recently developed technique for the characterization and quantification of myocardial deformation. By allowing measurement of the different components of myocardial deformation, it provides information which is not available with any of the currently used echocardiographic parameters, including LVEF. STE is a gray-scale based technique which is angle-independent and hence permits more comprehensive assessment of myocardial deformation. The STE software identifies these speckles and then tracks them frame-by-frame using a “sum-of-the absolute-differences' algorithm. From this data, the software automatically resolves the magnitude of myocardial deformation in different directions and generates strain and strain rate curves.[28] In the present study, we have not done STE as it was not available in our institute.

Conclusions

LV systolic dyssynchrony was more common in LBBB patients with LV dysfunction than those with normal LV function, irrespective of the presence or absence of HF. QRS duration and LV systolic dyssynchrony did not have any significant association in LBBB patients. TDI criteria may be useful to diagnose a patient with LV systolic dyssynchrony.